Promising antifungal activity of new oxadiazole against Candida krusei


Autoři: Daniella Renata Faria aff001;  Karina Mayumi Sakita aff001;  Isis Regina Grenier Capoci aff001;  Glaucia Sayuri Arita aff001;  Franciele Abigail Vilugron Rodrigues-Vendramini aff001;  Admilton Gonçalves de Oliveira Junior aff002;  Maria Sueli Soares Felipe aff003;  Patrícia de Souza Bonfim de Mendonça aff001;  Terezinha Inez Estivalet Svidzinski aff001;  Erika Seki Kioshima aff001
Působiště autorů: Department of Clinical Analysis and Biomedicine, Laboratory of Medical Mycology, State University of Maringá, Maringá, Paraná, Brazil aff001;  Department of Microbiology, Laboratory of Microbial Biotechnology, State University of Londrina, Londrina, Paraná, Brazil aff002;  Department of Cell Biology, Laboratory of Molecular Biology, University of Brasília, Brasília, Distrito Federal, Brazil aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227876

Souhrn

Candida krusei is one of the most common agents of invasive candidiasis and candidemia worldwide, leading to high morbidity and mortality rates. This species has become a problem due to its intrinsic resistance and reduced susceptibility to azoles and polyenes. Moreover, the number of antifungal drugs available for candidiasis treatment is limited, demonstrating the urgent need for the discovery of novel alternative therapies. In this work, the in vivo and in vitro activities of a new oxadiazole (LMM11) were evaluated against C. krusei. The minimum inhibitory concentration ranged from 32 to 64 μg/mL with a significant reduction in the colony forming unit (CFU) count (~3 log10). LMM11 showed fungicidal effect, similar to amphotericin, reducing the viable cell number (>99.9%) in the time-kill curve. Yeast cells presented morphological alterations and inactive metabolism when treated with LMM11. This compound was also effective in decreasing C. krusei replication inside and outside macrophages. A synergistic effect between fluconazole and LMM11 was observed. In vivo treatment with the new oxadiazole led to a significant reduction in CFU (0.85 log10). Furthermore, histopathological analysis of the treated group exhibited a reduction in the inflammatory area. Taken together, these results indicate that LMM11 is a promising candidate for the development of a new antifungal agent for the treatment of infections caused by resistant Candida species such as C. krusei.

Klíčová slova:

Antifungals – Antimicrobial resistance – Candida – Candida albicans – Candidiasis – Drug metabolism – Kidneys – Yeast


Zdroje

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